Volume expanders (or plasma volume expanders) are used in intravenous therapy for providing additional volume for the circulatory system, typically for fluid replacement, as the patient undergoes a medical procedure. Many volume expanders are typically based on solutions of dextrans of various molecular weights, but volume expanders can also include other biocompatible substances such as albumin.
Typical blood expanders used in clinical settings include normal saline, lactated Ringer's solution, albumin, and dextran. Dextran 40, as an example, is in widespread use as a volume expander. In addition to its volume-expanding effects, Dextran 40 is additionally able to improve microcirculation with a relatively low risk of antigenicity, and it can also be used with patients where there is a risk of thromboembolic complications. Dextran 40 has a molecular weight of 40 kDa, but other higher molecular weight dextrans, such as Dextran 70 and Dextran 75, are also used as volume expanders.
Blood volume measurement is important for the determination of proper drug dosing, pharmacokinetics, and blood pressure maintenance. Blood volume status and blood volume management are indicators of medical conditions such as end stage renal disease, acute kidney injury, chronic kidney disease, and acute blood loss. In addition, the evaluation of blood volume is important for dialysis patients since there are important implications with regard to the loss of blood volume while on dialysis. This is clinically important for the control of blood pressure and clinical outcomes in patients with end stage renal disease who require dialysis or renal replacement therapy for volume removal.
A commonly used technique for estimating blood volume is based on the indicator dilution technique in which an indicator molecule is mixed and distributed into an unknown volume. An identical amount of the indicator molecule is placed into a known volume. The unknown volume can be measured by comparing the concentration of the indicator between the known and unknown volume. A common indicator molecule is albumin labeled with various dyes, such as radioactive iodine, or the fluorescent dye indocyanine green (ICG). For example, Daxor Corporation (New York, N.Y.) has developed a device for measuring blood volume using albumin labeled with radioactive iodine as the tracer indicator. The use of ICG-labeled albumin as a tracer indicator has also been disclosed, with the ICG-labeled albumin measured by near infra-red absorption of the molecule. However, because albumin is also being cleared from the blood during the time that the test is being conducted, both the ICG and radiolabeled methods require a rapid succession of precisely timed blood draws in order to back calculate and estimate the peak concentration of the exogenously introduced albumin at the time when it was fully distributed throughout the vascular compartment. The process of taking a succession of five or more blood draws is logistically challenging in busy hospital and critical care environments. Additionally, radiolabeled albumin has a very limited shelf life, and use of radioactive materials requires special handling procedures, and limits the environments where both testing and analysis can occur.
Current technology does not permit a determination of the plasma volume expander concentration in the patient's plasma because the volume expanders do not include a detectable marker, such as a fluorescent label, which is capable of providing the timeliest data on concentration. This can have a significant impact on biometric parameters, such as glomerular filtration rate (GFR) an important kidney function parameter. For instance, blood loss can potentially lead to a reduction in GFR values, while the addition of excess plasma volume expander may exacerbate the reduction in GFR. Using current technology, a clinician can continue to administer a plasma volume expander to a kidney patient in an effort to maintain the plasma volume to the point where the GFR stops due to an elevated level of plasma volume expander beyond efficacious levels.
It will be readily appreciated that there is a clinical need to develop a minimally invasive method to accurately and inexpensively measure blood volume and critical organ function. The present invention is provided to solve the problems discussed above and other problems, and to provide advantages and aspects not provided by prior techniques. A full discussion of the features and advantages of the present invention is deferred to the following detailed description.